Association of alcohol use and multimorbidity among adults aged 40 years and above in rural South Africa

We assessed the prevalence of reported alcohol use and its association with multimorbidity among adults aged 40 years and above in a rural, transitioning South African setting. Findings could potentially inform alcohol interventions integration in the prevention and treatment of chronic conditions. We analysed data from the first wave of The Health and Ageing in Africa—a longitudinal Study in an INDEPTH community (HAALSI) nested within the Agincourt Health and Demographic Surveillance Systems, conducted between November 2014 and November 2015 (n = 5059). We computed descriptive statistics and performed univariate analysis to determine factors independently associated with multimorbidity. Age, Body Mass Index, education, sex, and household wealth status and variables with a p-value < 0.20 in univariate analysis were included in multivariable Modified Poisson regression models. Any factors with a p-value of < 0.05 in the final models were considered statistically significant. The first wave of HAALSI was completed by 5059 participants aged 40 years and above and included 2714 (53.6%) females. The prevalence of reported ever alcohol use was 44.6% (n = 2253) and of these 51.9% (n = 1171) reported alcohol use in the last 30 days. The prevalence of HIV multimorbidity was 59.6% (3014/5059) and for multimorbidity without HIV 52.5% (2657/5059). Alcohol use was associated with HIV multimorbidity among all participants (RR: 1.05, 95% CI: 1.02–1.08), and separately for males (RR: 1.05, 95% CI: 1.00–1.10) and females (RR: 1.06, 95%CI: 1.02–1.11). Similarly, alcohol use was associated with multimorbidity without HIV among all participants (RR: 1.05, 95% CI: 1.02–1.09), and separately for males (RR: 1.06, 95% CI: 1.00–1.12) and females (RR: 1.06, 95% CI: 1.01–1.11). Reported alcohol use was common and associated with HIV multimorbidity and multimorbidity without HIV among older adults in rural northeast South Africa. There is a need to integrate Screening, Brief Interventions, and Referral for alcohol Treatment in the existing prevention and treatment of multimorbidity in South Africa.


ICPSR
Inter-University Harmful alcohol use is a significant public health problem globally 1,2 . Excessive alcohol use (defined as the act of binge drinking that includes ≥ 4 drinks at once for women and ≥ 5 drinks at once for men) 3 has direct impact on health-related Sustainable Development Goal 3 (SDG 3) through infectious diseases (for example HIV 2,4,5 , TB, and viral hepatitis), Non Communicable Diseases (NCDs), and mental health. In 2016, approximately 49% of alcohol attributable Disability-adjusted life years (DALYs) were due to NCDs and mental health conditions. Moreover excessive alcohol use resulted in 1.7 million deaths from NCDs, while 12.9% deaths attributable to alcohol consumption were due to infectious diseases 2 .
Excessive alcohol use is increasing in Sub-Saharan Africa (SSA), resulting in substantial cognitive, behavioural, and physiological symptoms. Previous studies indicate that approximately 20% of all individuals attending healthcare facilities had alcohol use disorder (AUD) [6][7][8] . Despite the magnitude of this impact, Mushi et al. 9 found that only less than 1% of those with AUD were diagnosed and received appropriate treatment. Furthermore, a report by the World Health Organisation (WHO) showed that strategies to prevent excessive alcohol use and further interventions were scarce in SSA 2 as such there is no integration of alcohol use interventions like Screening, Brief Intervention and Referral for Treatment (SBIRT) in either primary health care (PHC) or in the management of multimorbidity 9,10 .
Multimorbidity is an escalating public health problem that poses significant impact on quality of life and resulting in increased health threats and financial burden to health systems and populations [11][12][13] . Alcohol use is one of the four major risk factors for multimorbidity 11,13,14 . The main clinical complications associated with excessive alcohol use include HIV, hypertension, diabetes, mental health, and liver fibrosis and cirrhosis [15][16][17][18][19][20][21][22][23][24] . This occurs mainly due to the toxic biochemical effects of alcohol that may increase the risk of organ damage, compromise treatment effectiveness, or even the safety of prescribed medications due to chemical interactions 25 .
Both excessive alcohol use and multimorbidity are recognised as significant problems in SSA 2 but their association has not been properly studied as well as their impact in rural African settings. This paper reports on the prevalence and association between reported alcohol use and multimorbidity (with and without HIV) among older adults aged ≥ 40 years in a rural South African setting. The study findings could potentially inform targeted alcohol reduction interventions amongst those most at risk, integration in multimorbidity prevention and treatment at PHC and community levels.

Methods
Study design, setting, and sample. The study used data from the baseline wave of the Health and Ageing in Africa-a longitudinal Study in an INDEPTH community (HAALSI) 26 . In brief, HAALSI is a longitudinal cohort study which recruited individuals aged ≥ 40 years who are enrolled in the Agincourt Health and Demographic Surveillance Systems (HDSS) and resident in the Bushbuckridge subdistrict of rural Mpumalanga, northeast South Africa. HAALSI aims to describe biological, social and economic determinants and consequences of health and ageing in rural South Africa 26 .The Agincourt HDSS, which is hosted by the South African Medical Research Council/Wits University Rural Public Health and Health Transitions Research Unit, has since 1992 collected longitudinal population-level data on vital demographic events (births, deaths, in-migration, and out-migrations) and other key health, social and economic indicators in the Agincourt study site 26 . Out of a total number of 12,875 eligible individuals from the Agincourt HDSS population, 6281 were randomly selected to participate in the HAALSI study, and 5059 (80.5%) completed the baseline wave. Data from all 5059 enrolled participants were analysed in our study.

Study visits.
Collection of data for the baseline wave of the HAALSI study took place between November 2014 and November 2015. Trained fieldworkers visited participants in their homes and collected data on sociodemographic variables and self-reported health status and risk factors using Computer-Assisted Personal Interviews (CAPI) and performed clinical assessments including blood pressure and point-of-care biomarkers. Dried blood spots were also collected for assessment of HIV serostatus and viral load. The survey instruments were translated from English into xi-Tsonga, the local language, and responses were back translated into English to ensure reliability. Translation was performed by experienced members of the unit staff with further minor modifications by the fieldworkers who conducted the interviews to ensure the language used was in keeping with the vernacular 26 .
Multimorbidity with HIV and multimorbidity without HIV. About a third of the participants in this study were living with HIV, as such in this study and the previous studies from the same cohort have classified multimorbidity into HIV multimorbidity and multimorbidity without HIV 37 . participants were considered to have HIV multimorbidity if they had two or more of these chronic illnesses including HIV 29,38,39 .We further classified the subset of individuals who presented more than one of the listed conditions but did not have HIV as one of their chronic conditions, as having multimorbidity without HIV. The chronic illnesses included were selected to ensure comparability with Health and Retirement Survey sister studies as well as to obtain further data on conditions which are prevalent in the Agincourt HDSS study area 26 . Statistical analysis. Data management pre-processing and analysis was conducted using STATA v17.0 (StataCorp, USA). The continuous variables (age and BMI) were categorised. The BMI was categorised according to WHO classification 28 , and all analyses were stratified by sex. Descriptive statistics were computed and reported as frequencies and proportions-this was done for sociodemographic factors, alcohol use patterns, and the prevalence of chronic conditions (both multimorbidity with HIV and multimorbidity without HIV patterns). The Chi 2 test was used to assess the strength of the association between individual sociodemographic and household factors and multimorbidity. Age, Body Mass Index, Wealth asset index and Educational attainment were considered as a priori confounders (for male and female models) and sex 40 (for all participants model) 41 and, therefore, added in the multivariable modified Poisson regression models regardless of the univariate p-values. All other variables were entered in the multivariable models if they had a p-value < 0.20 from the univariate analyses (Supplementary Tables 1-6). Furthermore, we have reported the Direct Acyclic Graph (DAG) on causal associations of alcohol use and multimorbidity (Fig. 1). We reported adjusted relative risk (RR) and their corresponding 95% confidence intervals (CI). Any factor with a p-value < 0.05 was considered statistically significantly associated with the outcomes of interest (multimorbidity with HIV or Multimorbidity without HIV).

Results
Study population characteristics. The HAALSI study randomly selected 6281 participants 40 years and older from the Agincourt HDSS. A total of 5059 (80.5%) were reachable, available, consented to take part, and were enrolled in the baseline wave of the study. From them 2345 were male (46.4%) and 2714 were female (53.6%). The more frequent age group was between the ages of 50-59 years old (n = 1410, 27.9%), a third had a normal BMI (n = 1719, 36.7%), and three quarters were not working (n = 3719, 73.7%). Almost half of them had no formal education (n = 2306, 45.7%) and lived in a 3-6-person household (n = 2438, 48.2%). A fifth of them belonged to households with the poorest wealth status (n = 1046, 20.7%) ( www.nature.com/scientificreports/ Prevalence of reported alcohol use and multimorbidity. Almost half of the participants (n = 2253, 44.6%) reported ever used alcohol, with half of them reporting alcohol use in the last 30 days (n = 1171, 51.9%).
Amongst those who reported alcohol use in the last 30 days the most frequent group were those who consumed alcohol at least once a week (n = 619, 52.9%), while the rest consumed it at least once a month. The overall prevalence of multimorbidity with HIV was 59.6% (n = 3014) and was similar in both males and females. The prevalence of multimorbidity without HIV was 52.5% (n = 2657) and was similar in males and females ( Table 2).
Alcohol use and HIV multimorbidity. Reported alcohol use was associated with HIV multimorbidity.
Other factors associated with HIV multimorbidity. Among all participants. Other factors that were significantly associated with HIV multimorbidity among all participants were BMI-specifically, the overweight category had a 10% higher risk (RR: 1.10, 95% CI: 1.05-1.16) and the obese category had a 12% higher risk (RR:1.12, 95%CI:1.09-1.16) compared to the normal weight category; marital status-especially in those reporting being separated or divorced (RR: 1.13, 95% CI: 1.05-1.22) and widowed (RR: 1.13, 95% CI: 1.05-1.21) in comparison to those who had never been married before. On the contrary, the following factors were found to be protective against HIV multimorbidity: education-specifically those who reporting completed secondary education or more had an 8% lower risk (RR: 0.92, 95% CI: 0.87-0.98) when compared to those who had no formal education; and individuals living in a 3-6-person household who had a 5% lower risk (RR: 0.95, 95% CI: 0.91-0.99) compared to those living alone.
Among females. Among females, other factors that were significantly associated with HIV multimorbidity were: marital status-those reporting being separated or divorced had a 14% higher risk (RR: 1.14, 95% CI: 1.03-1.25), whereas educational level had protective effect with those who completed secondary level or more having a 10% lower risk (RR: 0.90, 95% CI: 0.83-0.98).

Sensitivity analyses.
We performed a sensitivity analysis to assess the association between alcohol use and multimorbidity using these reported alcohol use frequency categories: "never", "ever", "at least once in the last 30 days", and "at least once a week". Similar results were obtained for both HIV multimorbidity and multimorbidity without HIV (Supplementary Tables 7 and 8). This was done to determine the impact of alcohol dose frequency on multimorbidity, and findings were similar to the presented alcohol use categories.

Discussion
We sought to determine the association between reported alcohol use and multimorbidity in a population of individuals aged ≥ 40 years in rural South Africa. In this analysis, we found that reported alcohol use was common with almost half of the population reporting ever used alcohol. Also, the reported alcohol use was modestly associated with HIV multimorbidity and multimorbidity without HIV. The observed prevalence of reported alcohol use in this study was 44.6%, which is similar to the WHO reported estimate of 43% among those aged 15 years and above in Africa 2,42 . In this study, across all alcohol use categories, males reported higher and more frequent alcohol consumption than females. Alcohol consumption is an activity dominated by males, with a prevalence reported to be 54% in males and 32% in females and mainly attributed to cultural roles of males and females 43 . www.nature.com/scientificreports/ The prevalence of multimorbidity with HIV in the study population was higher than that of multimorbidity without HIV (59.6% vs 52.5%) that is partly explained by the interaction of HIV with various NCDs. The overall prevalence of multimorbidity in this study is within the range of the previously reported prevalence of multimorbidity among older adults in South Africa (30-87%) and (0.7-81.3%) in Low-and Middle-Income countries 44,45 .
Reported ever use alcohol was associated with both multimorbidity with and without HIV in this study population (combination of both males and females), as well as only in females. This may have resulted from a visible dose-response of prior alcohol use that was ceased possibly due to efforts made by individuals to manage multimorbidity 25 . Previous studies on alcohol use and multimorbidity reported that alcohol use was associated www.nature.com/scientificreports/ with multimorbidity 11,25,46 and NCDs 13,14,47 , especially in the elderly 1,11,46,48,49 that could be mainly due to the toxic biochemical effects of alcohol 25 .
The association between reported alcohol use and both multimorbidity with and without HIV in males was not statistically significant. Other studies from high income countries reported a significant association of alcohol on NCDs in males and slightly beneficial for females-owing to the beneficial effect of light to moderate alcohol consumption on both diabetes and ischaemic disease 47 . These contradictions raise concerns to the accuracy of reporting of alcohol use in our study population pointing towards the likelihood of underreporting due to social desirability 50 .
Although non-significant, a more protective association was observed across the entire population of individuals who used alcohol in the last 30 days and both multimorbidity with and without HIV. This could be due to underreporting of alcohol use 50 .
Findings of this study should be interpreted with caution considering the following limitations: social desirability bias caused by underreporting of alcohol consumption patterns commonly occurs in multimorbid individuals-which, although uncertain, may have been the case in our study. If this was the case, this may have resulted in the underreporting of "ever" alcohol use by participants who were told to stop alcohol consumption due to the development of multimorbidity. These incidences of underreporting may have either biased the results towards the null or caused an overestimate of the effect. It is therefore critical to validate reported alcohol consumption using a biomarker especially in chronic diseases management settings. The cross-sectional nature of this study could not allow us to determine the directionality of causation between alcohol use and multimorbidity.
Overall, alcohol use is a significant problem in rural South Africa and globally. Alcohol use has been associated with chronic conditions and odds of having more than one chronic condition at a time (multimorbidity) in rural South Africa and elsewhere in Africa. Despite that, there has been no coordinated alcohol intervention response, with fragmented strategies being implemented across different governmental levels and departments 51 . Two scoping reviews reported on the lack of individual level interventions and integration of such interventions in primary health care settings in sub-Saharan Africa 9,10 .

Conclusion
Reported alcohol use and multimorbidity were common among adults in rural South Africa. Ever used alcohol was associated with both multimorbidity with and without HIV. Current alcohol use was not associated with multimorbidity potentially due to underreporting because of social desirability. There is an urgent need to integrate alcohol interventions in the management of NCDs and multimorbidity and such interventions should include an objective assessment of alcohol consumption.

Data availability
Data are available in a public, open access repository. Any additional data requests could be directed to chodziwadziwa.kabudula@wits.ac.za. The HAALSI baseline data are publicly available at the Harvard Centre for Population and Development Studies (HCPDS) programme website https:// haalsi. org/ data.